Prognostic value of high sensitivity troponin I in diabetic post-ACS patients

Serial Measurement of High Sensitivity Troponin I and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus in the EXAMINE Trial

Literature - Cavender MA, White WB, Jarolim R, et al. - Circulation 2017; published online ahead of print


High sensitivity cardiac troponin I (hsTnI) is useful for the identification of type 2 diabetes mellitus (T2DM) patients at high risk of cardiovascular (CV) events [1-3]. In the phase IIIb EXAMINE study, the CV safety of alogliptin, a non-selective DPP-4 inhibitor, was assessed in post-ACS patients (n=5380) with T2DM [4,5].

In this analysis of the EXAMINE study, the relationship of hsTnI changes (from baseline to six months) with outcome, as well as the CV safety of alogliptin in patients at highest CV risk were evaluated.

Main results

  • Patients with higher concentrations of hsTnI at baseline were older, more likely to be male, more likely to have a history of myocardial infarction (MI) as a qualifying event instead of unstable angina, had a longer duration of T2DM and higher incidences of renal dysfunction and heart failure.
  • hsTnI was detectable in 93% of patients, out of whom 16% had hsTnI elevated above the 99th percentile of the upper reference limit (URL).
  • The concentration of hsTnI at baseline was independently associated with the development of major CV events, while patients with hsTnI above the 99th percentile URL were at 3- to 9-fold higher risk of suffering a major CV event.
  • T2DM patients with hsTnI ≥1.9 ng/L to <26 ng/L had a 3-fold increased risk of CV death, MI, or stroke, compared with patients with undetectable hsTnI (11.5% vs. 4.1%, adjusted HR 2.86, 95% CI 1.41-5.78, P=0.004).
  • There was a strong positive, graded relationship between hsTnI at 6 months and the incidence of major CV events thereafter.
  • Based on the percentage change in hsTnI from baseline to 6 months, the majority of patients had either no change or a decline, while 21.5% of patients had at least 25% increase in hsTnI.
  • Baseline hsTnI and a history of heart failure were the only independent predictors of hsTnI change from baseline to 6 months (P<0.001 for both).
  • Compared with patients with consistently low hsTnI, clinically stable patients with hsTnI rising above the 99th percentile URL from baseline to 6 months were at increased risk for CV death, MI or stroke (28.1% vs. 8.8%, adjusted HR 2.65, 95%CI 1.64-4.28, P<0.001). Similarly, patients who had persistently elevated hsTnI were at higher risk for major CV events compared with patients with stable low hsTnI (22.5% vs. 8.8%, adjusted HR 1.90, 95% CI 1.33-2.70, P<0.001).
  • There was no evidence of either an increase or decrease in risk of CV death, MI or stroke with alogliptin compared with placebo in very high-risk CV patients identified by baseline hsTnI ≥ 26 ng/L (alogliptin vs. placebo 22.3% vs. 23.0%, HR 0.87, 95% CI 0.60-1.25, P=0.44).
  • The effects of alogliptin on CV death, MI or stroke were similar regardless of baseline hsTnI (P-interaction=0.80).


The majority of T2DM patients with established ischemic heart disease have detectable levels of hsTnI. The magnitude of hsTnI elevation is an independent predictor of both ischemic and heart failure events. Compared with placebo, alogliptin did not increase the risk of major CV events in patients at highest risk based on the degree of hsTnI elevation. These findings contribute to the understanding of the role of hsTnI as a predictor of major CV events in T2DM patients.


1. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503-2512.

2. Morrow DA, Cannon CP, Jesse RL, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes. Clin Chem. 2007;53:552-574.

3. Everett BM, Brooks MM, Vlachos HE, et al. Troponin and Cardiac Events in Stable Ischemic Heart Disease and Diabetes. N Engl J Med. 2015;373:610-620.

4. White WB, Bakris GL, Bergenstal RM, et al. EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J. 2011;162:620-626.

5. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327-1335.

Find this article online at Circulation

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